Lymphocytic cells are mainly responsible for immunity in organisms. Lymphocytic cells, which are all derived from the same stem cells in the blood, undergo repeated differentiation by the action of various differentiation-inducing factors or growth factors in the bone marrow or other organs, and are then released into the peripheral blood. Based on differences in differentiation, lymphocytic cells are roughly classified into B cells and T cells. It is believed that B cells have the ability of producing antibodies whereas T cells have the ability of presenting antigens, have a cytotoxic ability, and have various other abilities. When cells undergo tumorigenic transformation during the stage of differentiation, and start to grow abnormally in the bone marrow, lymphatic tissues and the peripheral blood, they become what are called lymphocytic tumors.
Because of the recent introduction of new technologies, specifically technological advances using monoclonal antibodies to differentiation antigens on the cell surface, it is now possible to identify the origin and/or the stage of lymphocytic cells. Currently, and for lymphocytic tumors as well, it is now possible to identify not only whether the origin of tumor cells is T cells or B cells but also the degree of maturity.
Based on the origin or the degree of maturity of tumor cells, lymphocytic tumors are roughly classified into the B cell tumors and the T cell tumors. B cell tumors are classified based on the degree of maturity into acute B lymphocytic leukemia (B-ALL), chronic B-lymphocytic leukemia (B-CLL), pre-B lymphoma, Burkitt lymphoma, follicular lymphoma, follicular pallial lymphoma, diffuse lymphoma, myeloma, and the like. T cell tumors are also classified based on the degree of maturity into acute T lymphocytic leukemia (T-ALL), chronic T lymphocytic leukemia (T-CLL), adult T cell leukemia (ATL), non-ATL peripheral T lymphoma (PNTL), and the like (Zukai Rinsho [Gan] (Clinical Illustrated [Cancer]), Series No. 17, Leukemia/Lymphoma, Takashi Sugimura et al., MEDICAL VIEW, 1987, B cell tumors, Kiyoshi Kouzuki, Nishimura Shoten, 1991).
Despite recent progress in medical technology, there is much to be desired in the treatment of lymphocytic tumors. For example, the cure rate of acute lymphocytic leukemia (ALL) is lower than 20%. In the case of lymphoma, the cure rate of B lymphoma is relatively high because of the progress in multiple-drug combination therapy, but the cure rate during the advanced stage is still about 50%. Further, T lymphoma is more refractory with the cure rate being about 30%, and less than 10% in adult T cell leukemia (ATL).
On the other hand, Goto, T. et al. have reported a monoclonal antibody (anti-HM1.24 antibody) that was obtained by immunizing mice with human myeloma cells (Blood (1994) 84, 1922-1930). When anti-HM1.24 antibody was administered to a mouse transplanted with human myeloma cells, the antibody accumulated in tumor tissues in a specific manner (Masaaki Kosaka et al., Nippon Rinsho (Japan Clinical) (1995) 53, 627-635), suggesting that anti-HM1.24 antibody could be applied in the diagnosis of tumor localization by radioisotopic labeling, missile therapies such as radiotherapy, and the like.
On the other hand, cancer patients often have decreased immunological functions. Since this is believed to be associated with carcinogenesis, attempts to improve these functions are being conducted. Biological response modifiers (BRM) serve to lead the direct and/or indirect response power of the organisms to tumors in a direction advantageous to the organisms, and this is used in the treatment. They mainly enhance the functions of macrophages, T cells and the like, and restore immunological ability and the like. In the days of treatment and research using non-specific immunity-activating substances, various cytokines were investigated for their biological activity and those that were found to be potentially effective were produced in large amounts (Konnniti no Tiryoyaku (Therapeutic Drugs of Today) (1995 edition), Yutaka Mizushima and Akimasa Miyamoto ed., Nankodo K.K., the 3rd printing of the 17th edition issued on Jun. 20, 1995).